Defining mechanisms for pancreatic beta-cell dysfunction in type 2 diabetes

Type 2 diabetes destroys the ability of pancreatic beta-cells to release insulin, and this project will track down the specific proteins responsible for that failure. The problem is that current treatments for type 2 diabetes manage symptoms rather than fix the underlying cellular defect. Human genetic studies have identified dozens of DNA regions linked to diabetes risk, but the proteins those regions control inside beta-cells remain largely unknown. Without knowing which proteins go wrong, researchers cannot design drugs that target the root cause. This project will use genome-scale techniques to identify the exact proteins at those genetic risk sites, then study their function in human beta-cell models grown in the lab. The goal is to map the networks these proteins operate in and pinpoint where insulin secretion breaks down. If successful, this work could reveal entirely new drug targets for type 2 diabetes. Because the approach starts with human genetics rather than animal models, the targets are more likely to translate into effective treatments. This is fundamental science with a clear path toward clinical application—understanding the molecular machinery of beta-cell failure is the necessary first step before any therapy can be designed.